Chronic, treatment-resistant depression and right fronto-striatal atrophy.

BACKGROUND Treatment-resistant depression (TRD) is relatively common but its neurobiological basis is poorly understood. Fronto-striatal structural brain changes have been reported in patients with depression but their association with treatment resistance and chronicity has not been established. METHOD Magnetic resonance images of 20 patients with TRD were compared with images of 20 recovered patients and 20 healthy controls. Images were compared using a voxel-based analysis (VBA) method; the results were validated by conventional volumetric analysis. The clinical associations of magnetic resonance imaging (MRI) changes with illness duration and severity were examined by VBA. RESULTS Only the TRD group exhibited right fronto-striatal atrophy, and subtle MRI changes in the left hippocampus on VBA. Atrophy was confirmed on volumetric analysis, the degree correlating with the cumulative number of electroconvulsive therapy (ECT) treatments received, suggesting an acquired deficit. CONCLUSIONS This is the first study to demonstrate fronto-striatal atrophy in patients with depression with poor outcome; the atrophy is more marked in those with more severe illness.

[1]  H. Mayberg Limbic-cortical dysregulation: a proposed model of depression. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[2]  Klaus P. Ebmeier,et al.  Clinical and psychometric correlates of dopamine D2 binding in depression , 1997, Psychological Medicine.

[3]  D. Weinberger,et al.  Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. , 1990, The New England journal of medicine.

[4]  E. Paykel Handbook of affective disorders , 1982 .

[5]  M. Annett A classification of hand preference by association analysis. , 1970, British journal of psychology.

[6]  D J Widlöcher,et al.  Psychomotor retardation: clinical, theoretical, and psychometric aspects. , 1983, The Psychiatric clinics of North America.

[7]  K. Krishnan,et al.  A magnetic resonance imaging study of putamen nuclei in major depression , 1991, Psychiatry Research: Neuroimaging.

[8]  M. LeMay,et al.  Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. , 1992, The New England journal of medicine.

[9]  H. Sackeim,et al.  Does ECT alter brain structure? , 1994, The American journal of psychiatry.

[10]  B. Roth,et al.  Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression∗ ∗ See accompanying Editorial, in this issue. , 1999, Biological Psychiatry.

[11]  N. Swerdlow,et al.  Dopamine, schizophrenia, mania, and depression: Toward a unified hypothesis of cortico-striatopallido-thalamic function , 1987, Behavioral and Brain Sciences.

[12]  Yvette I. Sheline,et al.  Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression , 1999, The Journal of Neuroscience.

[13]  G. Klerman,et al.  Long-term outcome of episodes of major depression. Clinical and public health significance. , 1984, JAMA.

[14]  Herbert Feistel,et al.  Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation—preliminary results , 1994, Biological Psychiatry.

[15]  N. Butters,et al.  Magnetic resonance imaging and mood disorders. Localization of white matter and other subcortical abnormalities. , 1995, Archives of general psychiatry.

[16]  M. Roth,et al.  The Diagnosis of Depressive Syndromes and the Prediction of E.C.T. Response , 1965, British Journal of Psychiatry.

[17]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[18]  P. Lavori,et al.  Recovery in major depressive disorder: analysis with the life table and regression models. , 1982, Archives of general psychiatry.

[19]  P. Fox,et al.  Cingulate function in depression: a potential predictor of treatment response , 1997, Neuroreport.

[20]  C. Coffey,et al.  Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. , 1993, Archives of general psychiatry.

[21]  J. Soares,et al.  The anatomy of mood disorders—review of structural neuroimaging studies , 1997, Biological Psychiatry.

[22]  J. Endicott,et al.  A diagnostic interview: the schedule for affective disorders and schizophrenia. , 1978, Archives of general psychiatry.

[23]  Klaus P. Ebmeier,et al.  Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression , 1998, British Journal of Psychiatry.